Genomic instability during reprogramming by nuclear transfer is DNA replication dependent.
Genomic instability during reprogramming by nuclear transfer is DNA replication dependent.
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DOI：
10.1038/ncb3485
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发表时间：
2017-04
影响因子：
21.3
通讯作者：
Egli D
中科院分区：
文献类型：
--
作者：
Chia G;Agudo J;Treff N;Sauer MV;Billing D;Brown BD;Baer R;Egli D
体细胞可以通过核转移到卵母细胞中而重新编程为多能状态，但发育停滞经常发生。虽然已知不完全转录重编程会导致发育失败，但重编程也涉及细胞周期进程和核结构的同步变化。在这里，我们研究了人类和小鼠核移植胚胎在胚胎基因组激活之前的细胞重编程事件。我们表明，遗传不稳定性标志着频繁的染色体分离错误和DNA损伤出现之前，并独立于转录活性。这些错误发生在DNA复制过渡之后，并由BRCA1修复。在没有有丝分裂核重构的情况下，DNA复制被延迟，错误在随后的有丝分裂中加剧。这些结果表明，独立于基因表达，细胞周期进程的细胞类型特异性特征构成了一个屏障，足以阻止重编程过程中从一种细胞类型过渡到另一种细胞类型。
Somatic cells can be reprogrammed to a pluripotent state by nuclear transfer into oocytes, yet developmental arrest often occurs. While incomplete transcriptional reprogramming is known to cause developmental failure, reprogramming also involves concurrent changes in cell cycle progression and nuclear structure. Here we study cellular reprogramming events in human and mouse nuclear transfer embryos prior to embryonic genome activation. We show that genetic instability marked by frequent chromosome segregation errors and DNA damage arise prior to, and independent of, transcriptional activity. These errors occur following transition through DNA replication and are repaired by BRCA1. In the absence of mitotic nuclear remodelling, DNA replication is delayed and errors are exacerbated in subsequent mitosis. These results demonstrate that independent of gene expression, cell-type-specific features of cell cycle progression constitute a barrier sufficient to prevent the transition from one cell type to another during reprogramming.
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影响因子：
64.8
作者：
Burrell RA;McClelland SE;Endesfelder D;Groth P;Weller MC;Shaikh N;Domingo E;Kanu N;Dewhurst SM;Gronroos E;Chew SK;Rowan AJ;Schenk A;Sheffer M;Howell M;Kschischo M;Behrens A;Helleday T;Bartek J;Tomlinson IP;Swanton C
通讯作者：
Swanton C
影响因子：
64.8
作者：
Dominguez-Sola, David;Ying, Carol Y.;Dalla-Favera, Riccardo
通讯作者：
Dalla-Favera, Riccardo
影响因子：
64.5
作者：
Lemaitre, JM;Danis, E;Méchali, M
通讯作者：
Méchali, M
影响因子：
64.8
作者：
MELLON, I;HANAWALT, PC
通讯作者：
HANAWALT, PC
影响因子：
21.3
作者：
Chan, Kok Lung;Palmai-Pallag, Timea;Hickson, Ian D.
通讯作者：
Hickson, Ian D.